Avenanthramide

Avenanthramides (Anthranilic acid amides) are a group of phenolic alkaloids found mainly in oats (Avena Sativa), but also present in white cabbage butterflies eggs (Pieris brassicae and P. rapae) and in fungus infected carnation (Dianthus caryophyllus).[1] A number of studies demonstrate that these natural products have anti-inflammatory, antioxidant, anti-itch, anti-irritant, and antiatherogenic activities.[2][3] Oat kernel extracts with standardized levels of Avenanthramides are ideal for skin, hair, baby and sun care products.[4][5] [6] [7] [8] [9] The name “Avenanthramides” was coined by Collins when he reported the presence of these compounds in oat kernels.[10] [11] It was later found that three avenanthamides were the open ring amides of Avenalumins I, II and III which were previously reported as oat phytoalexins by Mayama and co-workers.[12] [13]

Structure of Avenanthramide

History

Oat has been used for personal care purposes since antiquity. Indeed, wild oats (Avena sativa) was used in skin care in Egypt and the Arabian peninsula 2000 BC.[14] Oat bath was a common treatment of insomnia, anxiety and skin diseases such as eczema and burns.[14] In Roman times, its use as a medication for dermatological issues was reported by Pliny, Columella, and Theophrastus.[15] In the 19th century, oatmeal baths were often used to treat many cutaneous conditions, especially pruritic inflammatory eruptions. In the 1930s, the literature provided further evidence about the cleansing action of oat along with its ability to relieve itching and protect skin. In 2003, colloidal oatmeal was officially approved as a skin protectant by the FDA.[14] However, little thought had been given to the active ingredient in oats responsible for the anti-inflammatory effect until more attention was paid to avenanthramides which were first isolated and characterized in the 1980s, by Collins.[16] [17] Since then, many congeners have been characterized and purified and it is known that Avenanthramides have antioxidant, anti-inflammatory and anti-atherosclerotic properties and may be used as a treatment for people with inflammatory, allergy or cardiovascular diseases.[17] In 1999 studies made by Tufts University showed that avenanthramides are bioavailable and keep bioactive in humans after consumption.[17] More recent studies made by the University of Minnesota showed that the antioxidant and anti-inflammatory activities can be increased through the consumption of 0.4 to 9.2 mg/day of Avenanthramides during 8 weeks.[18] The International Nomenclature of Cosmetic Ingredients (INCI) originally called an oat extract with a standardized level of Avenanthramides as “Avena sativa kernel extract” however, recently, they also accepted the INCI name “Avenanthramides” to describe an extract containing 80% of these oat phenolic alkaloids.[18] [19]

Medical and personal care uses

Anti-inflammatory and Anti-itch activity

Studies made by Sur (2008) provide evidences that avenanthramides significantly reduce the inflammatory response. [20] Inflammation is a complex and self-protect reaction that occurs in the body against foreign substance, cell damage, infections, and pathogens. The inflammatory responses are controlled through a group called cytokines that is produced by the inflammatory cells.[21] Furthermore, the expression of cytokines are regulated through inhibition of Nuclear Transcription Factor Kappa B (NF-κB).[22] Many studies have demonstrated that Avenanthramides can reduce the production of pro-inflammatory cytokines such as IL-6, IL-8, and MCP-1 by inhibiting NF-κB activation that is responsible to activate the genes of inflammatory response.[20] Thus, these oat polyphenols mediate the decrease of inflammation by inhibiting the cytokine release.[20] In addition, it was found that avenanthramides inhibit neurogenic inflammation, which is defined as an inflammation triggered by the nervous system and causes vasodilatation, edema, warmth and hypersensitivity.[23] Also, Avenanthramides significantly reduce the itching response, and its efficiency is comparable to the anti-itch effect produced by hydrocortisone.[20]

Redness reduction

Avenanthramides have effective antihistaminic activity; it reduces significantly itch and redness compared with untreated areas.[24]

Suggested mechanism of action

According to Sur (2008) studies, the anti-inflammatory effect of the Avenanthramides is due to the inhibition of the NF-kβ activation in NF-kβ dependent cytokine.[20] Nuclear factor-kappa β (NF-κB) is responsible for regulate the transcription of DNA and participate on the activation of genes related to inflammatory and immune responses.[25] Consequently, suppressing the NF-κB limits the proliferation of cancer cells and reduces the level of inflammation.[25] Avenanthramides are able to inhibit the release of inflammatory cytokines that are present in pruritic skin diseases and may cause the itch sensations.[25] In addition, its anti-inflammatory activity may prevent the vicious itch scratch cycle and reduce the scratching-induced secondary inflammation that often occur in atopic dermatitis and eczema, preventing the skin from disrupting its barrier.[26] Avenanthramides also have a chemical structure similar to the drug Tranilast, which has anti-histaminic action. The anti-itch activity of avenanthramides may therefore be associated with the inhibition of histamine response.[27] Taken together, these results prove the effect of Avenanthramides as powerful anti-inflammatory agents and its importance in dermatologic applications.

Antioxidant activity

Avenanthramides are known to have potent antioxidant activity, acting primarily by donating a hydrogen atom to a radical. An antioxidant is: “any substance that, when present at low concentrations compared to those of an oxidisable substrate, significantly delays or prevent oxidation of that substrate” ( Halliwell, 1990). These phytochemicals are able to combat the oxidative stress present in the body that is responsible to cause cancer, and cardiovascular disease.[28] Among the avenanthramides there are different antioxidant capacities where C has the highest capacity, followed by B and A).[1]

Dietary supplement

Avenanthramides extracted from oats show potent antioxidant properties in vitro and in vivo, and according to studies made by Dimberg (1992), its antioxidant activity is many times greater than other antioxidants such as caffeic acid and vanillin.[16] Aven-C is one of the most significant avenanthramides present in the oats, and it is responsible for oats' antioxidant activity. The effects of the Avenanthramide-enriched extract of oats has been investigated in animals, and a diet of 20 mg Avenanthramide per kilogram body weight in rats has been shown to increase the superoxide dismutase (SOD) activity in skeletal muscle, liver, and kidneys, destroying harmful free radicals in the body and ensuring a long healthy life span by preventing the onset of a liver cancer, muscle mass loss, and earlier incidence of cataracts.[29] Also, a diet based on Avenanthramides enhances glutathione peroxidase activity in heart and skeletal muscles, protecting the organism from oxidative damages.[30]

Nomenclature

Avenanthramides consist of conjugate of one of three phenylpropanoids (p- coumaric, ferulic, or caffeic acid) and anthranilic acid (or a hydroxylated and/or methoxylated derivate of anthranilic acid)[1] Collins and Dimberg have used different system of nomenclature to describe the Avenanthramides in their publications. Collins assigned a system that classifies Avenanthramides using alphabetic descriptors. On the other hand, Dimberg assigned upper case letters to the anthranilate derivate and lower cases to the accompanying phenylpropanoid such as “c” for caffeic acid, “f” for ferulic acid, or “p” for anthranilic acid p-coumaric acid. Later, Dimberg’s system was modified to use a numeric descriptor for the anthranilic acid.)[1] The following avenanthramides are most abundant in oats: avenanthramide A (also called 2p, AF-1 or Bp), avenanthramide B (also called 2f, AF-2 or Bf), avenanthramide C (also called 2c, AF-6 or Bc), avenanthramide O (also called 2pd), avenanthramide P (also called 2fd), avenanthramide Q (also called 2 cd).

Structure of Avenanthramide
Collins Dimberg's original Dimberg's modified n R1 R2 R3 R4 R5
A Bp 2p 1 H OH H OH H
B Bf 2f 1 H OH OCH3 OH H
C Bc 2c 1 H OH OH OH H
O 2pd 2 H OH H OH H
P 2fd 2 H OH OCH3 OH H

Biosynthesis

There are evidences that the amount of avenanthramides found in the grains is related to genotype, environment, crop year and location, and tissue (Matsukawa et al., 2000). The environment factors are not clearly known, but it is believed that less avenanthramides are produced in the oats when they are grown in dry environments because it does not favor Crown Rust – a kind of fungus that had showed to stimulate avenanthramides production in oats grains.)[1]

Chemical stability

pH

Avenanthramides are not all as sensitive to pH and temperature. This was well illustrated in a study conducted on Avenanthramides A, B and C.)[1] In this study it was found that Avenanthramide A (2p) concentration was essentially unchanged in sodium phosphate buffer after three hours at room temperature or in a 95 °C. The Avenanthramides B (2f) appeared to be more sensitive to the higher temperature at pH 7 and 12. The Avenanthramides C (2c), in the contrast, underwent chemical reorganization at pH 12 at both temperature and diminished by more than 85% at 95C, even at pH 7 (Dimberg et al., 2001).)[1]

UV

Avenanthramides are also affected by ultra-violet (UV) light. Dimberg found that the 3 avenanthramides tested (A,B and C) remained in the trans conformation after 18 hours exposure to UV light at 254 nm. On the other hand, Collins reported that the avenanthramides isomerize upon exposure to daylight or UV light.)[1]

Synthetic Avenanthramides

Avenanthramides can be artificially synthesized. Avenanthramides A, B, D, and E were synthesized by Collins (1989), using chromatography methods, and adapting Bain and Smalley’s procedure (1968).[31] In all the 4 components it was found that the synthetic substances were identical to the ones extracted from oats.[11] Dihydroavenanthramide (DHAvn) is another synthetic derivative of Avenanthramides. It has been developed as a drug and, like natural avenanthramides, it helps to reduce symptoms such as itching, redness, and wheals. Tests showed that it also increases resistance of RINm5F cells and pancreatic islets to cytokine-induced toxicity while decreasing β-cell destruction, and maintaining normal insulin secretion capacity. In vivo, pre-treatment of mice with DHAvn blocked the development of Type 1 diabetes. These findings suggest that this synthetic substance also has benefits to human health.[32]


References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Chu Y. (2014). "Oats nutrition and technology". (1 edition). Wiley Blacwell
  2. ↑ Koening, R.T., Dickman, J.R., Wise, M.L., Ji,L.L. (2011). "Avenanthramides Are Bioavailable and Accumulate in Hepatic,Cardiac, and Skeletal Muscle Tissue Following Oral Gavage in Rats". Journal of Agricultural and food chemistry, 6438 – 6443
  3. ↑ Kurtz, E.S.; Wallo, W. "Colloidal oatmeal: history, chemistry and clinical properties". Journal Drugs Dermatol. 2007,6,167-170
  4. ↑ Ceapro Inc, Canada. CP Oat Avenanthramide Extract. Available at: http://ceapro.com/wp-content/uploads/2012/09/CPOatAvenanthramideExtract-902-3043-Jun-131.pdf . Accessed at August, 10th of 2014.
  5. ↑ Oat cosmetics – Advancing Oat Technology. CP Oat Avenanthramides. Available at: http://oat.co.uk/ingredients-formulations/oat-av/. Accessed at August, 10th of 2014.
  6. ↑ Oat cosmetics – The natural ingredient house. CP Oat Avenanthramides. Available at: https://www.in-cosmetics.com/__novadocuments/2746. Accessed at August, 10th of 2014.
  7. ↑ Agriculture and Agri-Food Canada (2013). Innovation Express Vol.4 No 2. Available at: http://www.agr.gc.ca/eng/science-and-innovation/science-publications-and-resources/innovation-express-magazine/innovation-express-volume-4-no-2-2013/?id=1372115512470. Accessed at August, 11th of 2014
  8. ↑ Cosmetic & Toiletries – Science Applied. CP Oats Avenanthramides. Available at: http://dir.cosmeticsandtoiletries.com/detail/tradeName.html?id=20310. Accessed at August 11th of 2014.
  9. ↑ AveenoMD Active naturals (2014). Oats. Available at: https://www.aveenomd.com/active-naturals-ingredients/oats. Accessed at August 11th of 2014.
  10. ↑ Collins FW and Mullin WJ (1988) "High-performance liquid chromatographic determination of avenanthramides, N-aroylanthranilic acid alkaloids from oats". Journal of Chromatography A, 445, 363-370
  11. ↑ 11.0 11.1 "Oat phenolics: avenanthramides, novel substituted N-cinnamoylanthranilate alkaloids from oat groats and hulls". Journal of Agriculture and Food Chemistry 37, 60-66.
  12. ↑ Mayama S, Tani T, Matsuura Y, Ueno T. and Fukami H. (1981) "The production of phytoalexins by oat in response to Crown Rust, Puccina coronate f. sp. Avenae". Physiological Plant Pathology 19, 217-226.
  13. ↑ Crombie L and Mistry J. (1990) "The phytoalexins of oat leaves: 4-3,1-benzoazin-4-onmes or amides?" Tetrahedron Lettres 31, 2647-2648.
  14. ↑ 14.0 14.1 14.2 "Less-known botanical cosmeceuticals". Dermatologic Therapy, Vo. 20, 330-342
  15. ↑ Melardi MG. (2013) "Avena". Available at: http://www.lapelle.it/alimentazione/avena.htm
  16. ↑ 16.0 16.1 Dimberg LH. Theander O, Lingnert H. "Avenanthramides - a group of phenolic antioxidants in oats". Cereal Chem. 1992;70:637–641.
  17. ↑ 17.0 17.1 17.2 Carder G., Chu, Y. Chung, Y. French, J.A., O'Shea, M., Jan-Willem, B.K. (2013). U. S. Patent No. 833,717. Chicago, IL (US), "United States Patent Application Publication".
  18. ↑ 18.0 18.1 Chatel, R.E., Chu, Y.F., Chung, Y., French, J.A., O'Shea, M., (2013). Publication number US20130183405 A1. "Method of Processing Oats to Achieve Oats with an Increased Avenanthramide Content".
  19. ↑ Fowler, J. J., (2007) "Examining options for Barrier Protection in Atopic Dermatitis and Eczema". Clinical update – Recent insights into the origin and management of atopic dermatitis. Supported by Johnson & Johnson.
  20. ↑ 20.0 20.1 20.2 20.3 20.4 Sur, R., Nigam, A., Grote, D., Liebel, F., Southall, M., D. (2008). "Avenanthramides, polyphenols from oats, exhibit anti-inflammatory and anti-itch activity". Arch Dermatol Res, 300:569–574
  21. ↑ Kim, E.O., Min, K.J, Know, T.K., Um, B.H., Moreau, R. H., Choi, S.W.(2012) "Anti-inflammatory activity of hydroxycinnamic acid derivatives isolated from corn bran in lipopolysaccharide-stimulated" Raw 264.7 macrophages. Elsevier, 1309-1316.
  22. ↑ Chu, Y.F., Wise, M.L., Gulvady, A.A., Chang, T., Kendra, D.F., Klinken, B.J.V., Shi, Y., O’Shea, M. (2013). "In vitro antioxidant capacity and anti-inflammatory activity of seven common oats". Elsevier, 426-431.
  23. ↑ Meggs WJ. (1993). "Neurogenic Inflammation and Sensitivity to Environmental Chemicals". Environmental Health Perspectives, Volume 101.
  24. ↑ Eichenfield, L., Fowler, J., Jr. Recent Insights into the Origin and Management of Atopic Dermatitis. Skin & Allergy News.
  25. ↑ 25.0 25.1 25.2 Lippert U, Hoer A, Moller A, Ramboer I, Cremer B, Henz BM., (1998). "Role of antigen-induced cytokine release in atopic pruritus". Int Arch Allergy Immunol 116:36-39
  26. ↑ Schmelz M., Handwerker H.O. (2003) "Neurophysiologic basis of itch". In: Yosipovitch G., Greaves M.W., Fleishcer A.B., McGlone F. (eds) "Itch basic mechanisms and therapy". Marcel Dekker, New York, pp 5-20.
  27. ↑ Guo W, Wise ML, Collins FW, Meydani M (2008) "Avenanthramides, polyphenols from oats, inhibit IL-1beta-induced NF-kappaB activation in endothelial cells". Free Radic Biol Med 44:415–429
  28. ↑ Adom, K.K., Liu, R.H. (2002). "Antioxidant activity of grains". Journal of Agricultural and food chemistry, 50, 6182- 6187.
  29. ↑ Bloom RZ. (2009). "Antioxidant and Anti-proliferative Properties of Selected Grape Seed Extracts". ProQuest, 13-16.
  30. ↑ Meydani, M. (2009). "Potential health benefits of avenanthramides of oats". Nutrition Reviews, Vo. 67, 731-735.
  31. ↑ Bain D., Smalley R. K. "Synthesis of 2-substituted-4(H)-3.1-benzoxazin-4-ones". J. Chem. Soc. C. 1968, 1593-1597.
  32. ↑ Lv N., Song M., Lee Y., Choi H., Kwon K., Park J., Park B. (2009). "Dihydroaventhramide D protects pancreatic β-cells from cytokine and streptozotocin toxicity". Biochemical and Biophysical Research Communications, 387, 97-102.